| Summary: | 碩士 === 國防醫學院 === 藥理學研究所 === 86 === The rostral ventrolateral medulla (RVLM) and nucleus tractus solitarii (NTS) are two important brain stem nuclei in central cardiovascular regulation. The neurons in RVLM project to presympathetic neurons of spinal cord and maintain the sympathetic nerve activity, whereas NTS integrates peripheral messages and modulates the reflex activity of cardiovascular effects.Nitric oxide (NO) is a remarkable regulation molecule which plays an important role in multiple physiological functions. In this study, we examined the cardiovascular effects of NO in RVLM of rats, and the role of NO in modulating the baroreflex in NTS of hypertensive rats. The cardiovascular effects of NO in RVLM of Sprague-Dawley rats (250-350 g) were investigated. Drugs were applied to the RVLM or NTS by sterotaxic microinjection technique and their cardiovascular effects were evaluated. The role of NO in baroreflex response was evaluated in SD and 2K1C rats, which were established by clamping the left renal arte ry of SD rats (180-200 g) with a silver clip. The induced elevation in blood pressure and the decrease in heart rate, caused by phenylephrine injections, were used to calculate the index of baroreflex sensitivity. We observed that unilateral microinjection of L-arginine (90 nl) into the RVLM produced obvious depressor effects. However, D-arginine and L-NMMA (a NO synthase inhibitor) had no significant cardiovascular effects. Pretreatment of L-arginine attenuated the pressor effect of L-glutamate, while pretreatment of D-arginine or L-NMMA did not. Microinjection of L-arginine reduced the pressor effect of NMDA, but not that of AMPA (non-NMDA receptor agonist). In the RVLM, the depressor effect of GABA was reduced by pretreatment of L-arginine, but not by D-arginine or L-NMMA. The depressor effect of baclofen (GABAB receptor antagonist), but not that of muscimol (GABAA receptor antagonist), was attenuated by L-arginine. 2K1C rats had an elevated plasma NO level at 1 week (1W) and returned to normal at 4 weeks (4W) after operation, compared to values of SD rats. Significant hypertension was observed 4W but not 1W after operation. The baroreflex sensitivities of 2K1C rats (1W, 4W) were lower than that of SD rats. Microinjection of ADMA (an endogeneous NOS inhibitor) attenuated the baroreflex sensitivity in S D rats, but not the sensitivity of 2K1C rat (4W). In conclusion, our data suggest that NO may produce direct depressor effect in RVLM, and may be involved in cardiovascular regulation by modulating the effects of glutamate and GABA. Secondly, the loss of NO-dependent component of baroreflex may be the cause of reduced barorelfex sensitivity in 2K1C rats. The results show that NO plays an important role in the cardiovascular regulation of RVLM and NTS.
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